The processing of biological fluid such as blood or blood components typically involves using a reusable processing machine (“hardware”) and a disposable fluid circuit adapted for mounting or other association with the reusable apparatus. The fluid circuit typically includes (plastic) bags and associated tubing that defines a flow path through the circuit. The disposable fluid circuit may also include one or more separation devices where the biological fluid/cells can be separated into two or more components, washed or otherwise processed. Separation devices may separate the biological fluid based on centrifugal separation and/or, as described below, membrane separation.
Conventionally, the biological fluid to be processed is contained in one or more source containers (or bags), which source containers are attached to the disposable fluid circuit and then drawn through the disposable fluid circuit as the biological fluid is processed using the one or more separation devices. Ultimately, cells are collected in another container, referred to as the product container (or bag), which is removed or separated from the disposable fluid circuit when the processing has been completed.
As an initial step in the processing, the operator will sample the biological fluid in the one or more source bags to determine the starting cell concentration of a particular type of cell in the bag. If there is more than one source bag, then the operator will sample each individual bag to determine a starting cell concentration for the cells of interest in that bag. In fact, if there is more than one source bag, the operator will typically calculate a starting number of cells using the starting cell concentrations for each of the source bags.
The starting number of cells of interest is particularly important to the operator as the operator typically will need to input the desired volume in the product bag prior to initiating the processing of the biological fluid, the desired volume selected to achieve a specific concentration of the cells of interest in the product bag. The cell concentration in the product bag is a function of the volume in the product bag and the number of cells present in the product bag. In addition, it will be recognized that the number of cells present in the product bag is a function of the number of cells present in the source bag(s).
To determine the number of cells expected to be present in the product bag, the operator may simply assume full recovery of all of the cells initially present in the product bag. Alternatively, the operator may assume a particular recovery percentage based on historical data. In any event, some assumption is typically made about the effect of processing on the initial number of cells to arrive at the expected number of cells present in the product bag at the end of processing.
Such a method of operation presents several challenges for the operator. For example, the volume within the source bag(s) is often very large, with the consequence that the cell count from the sample taken may not be fully representative of the cell concentration in all regions of the source bag. Further, when there are multiple bags involved, the effects of sampling variations between the bags contribute to further uncertainly in the initial cell count. Even if it were possible to achieve a very representative initial cell count, the assumptions made regarding the effect of the processing on the cell count in the product bag increase the uncertainty of the calculation of the volume required to result in the desired final cell concentration. As such, the final volume selected for the product bag by the operator will likely result in a cell concentration that differs from the desired.